1. Field of the Invention
The invention relates to the enzymatic synthesis of optically active hydroxamic acids and to their conversion to optically active primary amines by a Lossen rearrangement.
2. Background of the Prior Art
Hydroxamic acids are compounds of great pharmaceutical interest. Hydroxamic acid derivatives exist which have antibacterial and fungicidal properties (Duda et al., 1965; Hase et al., 1971). Alkylaminopropionohydroxamic acids exhibit hypotensive properties (Coutts et al., 1971). Hypocholesterolaemic actions have also been demonstrated for hydroxamic acids (Ludwig et al., 1967). p-Butoxyphenylacetohydroxamic acid possesses an anti-inflammatory action (Dell et al., 1971) and is used in human medicine. Some hydroxamic acids have been studied for their efficacy against malaria (Hynes, 1970; Hynes & Hack, 1972).
Enantiomerically pure hydroxamic acids, however, are of particular importance. Their pharmacological activity is higher than that of the racemates. Furthermore, via the Lossen rearrangement, they also open up a new route to chiral primary amines. This class of substances is pharmacologically of great importance as well. Thus chiral .beta.-amino alcohols, for example, are used in large amounts as .beta.-adrenoceptor antagonists, abbreviated to .beta.-blockers.
However, the preparation of enantiomerically pure hydroxamic acids by the conventional methods of organic chemistry is expensive. It normally requires a racemate separation or the use of metal-organic catalysts, but the latter are generally unsuitable for the preparation of drugs. Such methods are described for example in DE-PS 2 400 531, EP-A-203 379 and EP-A-268 215.